A5007906768- Congenital heart defects research
- Cardiomyopathy and Myosin Studies
- Cell Image Analysis Techniques
- Cardiac electrophysiology and arrhythmias
- Single-cell and spatial transcriptomics
- Tissue Engineering and Regenerative Medicine
- Animal Behavior and Reproduction
- Viral Infections and Immunology Research
- Cardiovascular Effects of Exercise
- Cellular Mechanics and Interactions
- Molecular Biology Techniques and Applications
- Receptor Mechanisms and Signaling
- Cardiac Fibrosis and Remodeling
- RNA Research and Splicing
- Extracellular vesicles in disease
- Telomeres, Telomerase, and Senescence
- Mesenchymal stem cell research
- Endoplasmic Reticulum Stress and Disease
- Physiological and biochemical adaptations
- Angiogenesis and VEGF in Cancer
- Congenital Heart Disease Studies
- COVID-19 diagnosis using AI
- Olfactory and Sensory Function Studies
- Cardiac Ischemia and Reperfusion
- Adolescent Sexual and Reproductive Health
Imperial College London
2020-2025
Lung Institute
2023
British Heart Foundation
2022
University of Oxford
2015-2022
University of Algarve
2005-2007
Pathogenic variants in genes that cause dilated cardiomyopathy (DCM) and arrhythmogenic (ACM) convey high risks for the development of heart failure through unknown mechanisms. Using single-nucleus RNA sequencing, we characterized transcriptome 880,000 nuclei from 18 control 61 failing, nonischemic human hearts with pathogenic DCM ACM or idiopathic disease. We performed genotype-stratified analyses ventricular cell lineages transcriptional states. The resultant atlas demonstrated distinct...
The function of a cell is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here we combine single-cell spatial transcriptomics data to discover cellular niches within eight regions human heart. We map cells microanatomical locations integrate knowledge-based unsupervised structural annotations. also profile cardiac conduction system
The mammalian heart is derived from multiple cell lineages; however, our understanding of when and how the diverse cardiac types arise limited. We mapped origin embryonic mouse at single-cell resolution using a combination transcriptomic, imaging, genetic lineage labeling approaches. This mapping provided transcriptional anatomic definition progenitor types. Furthermore, it revealed pool that anatomically transcriptionally distinct currently known progenitors. Besides contributing to...
The mammalian heartbeat is thought to begin just prior the linear heart tube stage of development. How initial contractions are established and downstream consequences earliest contractile function on cardiac differentiation morphogenesis have not been described. Using high-resolution live imaging mouse embryos, we observed randomly distributed spontaneous asynchronous Ca2+-oscillations (SACOs) in forming crescent (stage E7.75) overt beating. Nascent contraction initiated at around E8.0 was...
The urine of freshwater fish species investigated so far acts as a vehicle for reproductive pheromones affecting the behaviour and physiology opposite sex. However, role urinary in intra-sexual competition has received less attention. This is particularly relevant lek-breeding species, such Mozambique tilapia (Oreochromis mossambicus), where males establish dominance hierarchies there possibility chemical communication modulation aggression among males. To investigate whether use during...
SUMMARY The current study investigated whether discrimination of sexual status female tilapia by males is mediated olfaction. Size-matched groups were assigned as pre- or post-ovulatory according to the time since their last ovulation (15-19 days pre-ovulatory, N=7; 1-3 post-ovulatory, N=8). Female-conditioned water and body fluids(urine, bile, faeces plasma) assessed for olfactory potency in recording electro-olfactogram (EOG). Water extracts, urine from pre-ovulatory females all evoked...
Abstract Obesity is linked to limited adipose tissue (AT) remodeling capacity, leading hypertrophic adipocytes, senescence, and inflammation. We used a mouse model expressing mTert (p21 +/Tert ) from the Cdkn1a locus investigate role of mTERT in obesity-induced metabolic disorders. Conditional expression reduces disorders associated with obesity. In AT, this accompanied by decrease number senescent p21-positive cells, very short telomeres, oxidative DNA damage. Single nucleus RNA-seq data...
Epithelial cells form diverse structures from squamous spherical organoids to densely packed pseudostratified tissues. Quantification of cellular properties in these contexts requires high-resolution deep imaging and computational techniques achieve truthful three-dimensional (3D) structural features. Here, we describe a detailed step-by-step protocol for sample preparation, deep-learning-assisted cell segmentation accurate quantification fluorescently labelled individual 3D within live We...
The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data donor tissue with spatial stratifying histopathological stages diffuse damage. We identify in composition across progressive damage, including waves molecularly distinct macrophages depletion epithelial endothelial populations. Predicted markers pathological...
Abstract Pathogenic variants in genes that cause dilated (DCM) and arrhythmogenic cardiomyopathies (ACM) convey high risks for the development of heart failure (HF) through unknown mechanisms. Using single nucleus RNA sequencing (snRNAseq), we characterized transcriptome 880,000 nuclei from 18 control 61 failing, non-ischemic human hearts with pathogenic DCM ACM or idiopathic disease. We performed genotype-stratified analyses ventricular cell lineages transcriptional states. The resultant...
Abstract A cell’s function is defined by its intrinsic characteristics and niche: the tissue microenvironment in which it dwells. Here, we combine single-cell spatial transcriptomic data to discover cellular niches within eight regions of human heart. We map cells micro-anatomic locations integrate knowledge-based unsupervised structural annotations. For first time, profile cardiac conduction system, revealing their distinctive repertoire ion channels, G-protein coupled receptors, cell...
Ischemic heart disease remains the foremost cause of death globally, with survivors at risk for subsequent failure. Paradoxically, cell therapies to offset cardiomyocyte loss after ischemic injury improve long-term cardiac function despite a lack durable engraftment. An evolving consensus, inferred preponderantly from non-human models, is that transplanted cells benefit via early paracrine signals. Here, we tested impact signals on human cardiomyocytes, using pluripotent stem cell-derived...
The heart is one of the first organs to develop during mammalian embryogenesis. In mouse, it starts form shortly after gastrulation, and derived primarily from embryonic mesoderm. unique in having perform a mechanical contractile function while undergoing complex morphogenetic remodelling. Approaches imaging morphogenesis activity developing are important understanding not only how this remodelling controlled but also origin congenital defects. Here, we describe approaches for visualising...
ABSTRACT The asymmetric morphology of the mammalian heart is essential to its function as organ pulmonary and systemic double circulation. Left-right asymmetry established by a leftward flow in node that results expression Nodal . This triggers cascade downstream genes, such Pitx2c , lateral plate mesoderm gives rise first morphologically recognizable primordial structure, cardiac crescent. Relatively little known about gene asymmetries crescent might underpin morphogenesis. To...
ABSTRACT Advances in fluorescence microscopy approaches have made it relatively easy to generate multi-dimensional image volumes and highlighted the need for flexible analysis tools extraction of quantitative information from such data. Here we demonstrate that by focusing on simplified feature-based nuclear segmentation probabilistic cytoplasmic detection can create a tool is able extract geometry based diverse mammalian tissue images. Our open-source platform, called ‘SilentMark’ cope with...
ABSTRACT POPDC2 encodes for the Popeye domain-containing protein 2 which has an important role in cardiac pacemaking and conduction, due part to its cAMP-dependent binding regulation of TREK-1 potassium channels. Loss Popdc2 mice results sinus pauses bradycardia morpholino knockdown popdc2 zebrafish atrioventricular (AV) block. We identified bi-allelic variants 4 families that presented with a phenotypic spectrum consisting node dysfunction, AV conduction defects hypertrophic cardiomyopathy....
Advances in fluorescence microscopy approaches have made it relatively easy to generate multi-dimensional image volumes and highlighted the need for flexible analysis tools extraction of quantitative information from such data. Here we demonstrate that by focusing on simplified feature-based nuclear segmentation probabilistic cytoplasmic detection can create a tool is able extract geometry-based diverse mammalian tissue images. Our open-source platform, called ‘SilentMark’, cope with...
Copyright information: Taken from Male urine signals social rank in the Mozambique tilapia ()http://www.biomedcentral.com/1741-7007/5/54BMC Biology 2007;5():54-54.Published online 12 Dec 2007PMCID:PMC2222621.e behaviour, aggressive displays and high aggression. Different letters over bars indicate significant differences (repeated-measures analysis of variance (ANOVA), = 125.6, < 0.001 followed by least difference (LSD) pairwise comparisons, 0.05).
<h3>Introduction</h3> Doxorubicin (Dox) is by far the most notorious cardio-toxic chemotherapy drug, which hampers its clinical use in treating breast cancer, lymphoma and leukaemia. It has been decades since Dox cardiotoxicity was revealed, but cellular molecular mechanisms have not fully elucidated. Here, we performed single-nucleus transcriptomic profiling on hearts from Dox-treated mice to explore how changes landscape signatures heart, with a focus cardiomyocytes (CM). <h3>Methods</h3>...
Abstract The most common cause of death due to COVID-19 remains respiratory failure. Yet, our understanding the precise cellular and molecular changes underlying lung alveolar damage is limited. Here, we integrate single cell transcriptomic data donor lungs with spatial stratifying histopathological stages diffuse (DAD). We identify in composition across progressive DAD, including waves molecularly distinct macrophages depleted epithelial endothelial populations throughout different types...